1-Methylpyrrolidine → HCID 71736063, compound

HRID 715148Notes

Reaction equation

HRID 715148 reaction equation
[CH3:1][N:2]1CCC[CH2:3]1.C=C([O:10][C:11](=O)[NH:12][C:13]1[CH:22]=[C:21]2[C:16]([CH:17]=[C:18]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[C:26]([NH:31][C:32]([NH:34][CH2:35][CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:33])[CH:25]=3)[C:19]([CH3:23])=[N:20]2)=[CH:15][N:14]=1)C.Cl.CNC>O1CCOCC1>[CH3:39][C:37]([CH3:38])([CH3:40])[CH2:36][CH2:35][NH:34][C:32](=[O:33])[NH:31][C:26]1[CH:25]=[C:24]([C:18]2[C:19]([CH3:23])=[N:20][C:21]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:12][C:11](=[O:10])[N:2]([CH3:3])[CH3:1])[CH:22]=3)[CH:29]=[CH:28][C:27]=1[F:30]

Participants

5

Reactant 3

HCID 84541-MethylpyrrolidineHCID 10473Dimethylamine, hydrochlorideHCID 89827818HCID 89827818, compound

Product 1

HCID 71736063HCID 71736063, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

Add 1-methylpyrrolidine (0.355 mL, 3.34 mmol) to a suspension of prop-1-en-2-yl(3-(3-(3-(3,3-dimethylbutyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)carbamate (0.2 g, 0.417 mmol) and dimethylamine hydrochloride (0.136 g, 1.668 mmol) in dioxane (4 mL) and heat at 60° C. overnight. Cool to RT, add satd. NaHCO3, extract with EtOAc (3×), dry the combined organics over MgSO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford 3-(3-(3-(3-(3,3-dimethylbutyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)-1,1-dimethylurea (99 mg, 51%). MS(ESI) m/z: 467.3 (M+H+). Treat the solid with MeCN (2 mL), add 0.1N HCl (2.33 mL, 0.233 mmol), freeze, lyophilize and dry to afford the title compound (76 mg, 71%). 1H NMR (400 MHz, DMSO-d6): δ 9.52 (s, 1H), 9.30 (s, 1H), 8.64 (s, 1H), 8.50 (s, 1H), 8.41 (s, 1H), 8.32 (dd, J=7.9, 2.4 Hz, 1H), 7.35 (dd, J=11.3, 8.4 Hz, 1H), 7.07 (m, 1H), 6.66 (m, 1H), 3.08 (m, 2H), 3.00 (s, 6H), 2.70 (s, 3H), 1.34 (m, 2H), 0.88 (s, 9H); MS(ESI) m/z: 467.3 (M+H+).

Workup

  1. temperatureCool to RT
  2. additionadd satd
  3. extractionNaHCO3, extract with EtOAc (3×)
  4. dry with materialdry the combined organics over MgSO4
  5. concentrationconcentrate to dryness
  6. custompurify via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-a92e1783391649b2ba3555b1972d145c
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

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